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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#1
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28988693/circulating-cd8-cd28-suppressor-t-cells-tied-to-poorer-prognosis-among-metastatic-breast-cancer-patients-receiving-adoptive-t-cell-therapy-a-cohort-study
#2
Qingkun Song, Jun Ren, Xinna Zhou, Xiaoli Wang, Guohong Song, Amy Hobeika, Yanhua Yuan, Herbert Kim Lyerly
BACKGROUND AIMS: This study aimed to determine the prognostic value of circulating CD8(+)CD28(-) T lymphocytes among breast cancer patients treated with adoptive T-lymphocyte immunotherapy after chemotherapy. METHODS: Two hundred and thirty-two breast cancer patients underwent adoptive T-cell immunotherapy. Circulating CD8(+)CD28(-) proportion was measured by flow cytometry. Median proportion of CD8(+)CD28(-) was 24.2% and set as the categorical cutoff value for further analysis...
October 4, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28982863/effects-of-adam10-and-adam17-inhibitors-on-natural-killer-cell-expansion-and-antibody-dependent-cellular-cytotoxicity-against-breast-cancer-cells-in-vitro
#3
Dang-Huan Pham, Ju-Sun Kim, Sang-Ki Kim, Dong-Jun Shin, Nguyen-Thanh-Tung Uong, Hoon Hyun, Mee Sun Yoon, Sin Jae Kang, Young Jae Ryu, Jin Seong Cho, Jung Han Yoon, Ji Shin Lee, Duck Cho, Soo-Hyeon Lee, Min Ho Park
BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28979132/impact-of-the-tumor-microenvironment-on-tumor-infiltrating-lymphocytes-focus-on-breast-cancer
#4
REVIEW
Ivan J Cohen, Ronald Blasberg
Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration-approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28978072/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#5
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969075/bptf-inhibits-nk-cell-activity-and-the-abundance-of-natural-cytotoxicity-receptor-co-ligands
#6
Kimberly Mayes, Zeinab Elsayed, Aiman Alhazmi, Michael Waters, Suehyb G Alkhatib, Mark Roberts, Carolyn Song, Kristen Peterson, Vivian Chan, Nikhil Ailaney, Pumoli Malapati, Tana Blevins, Berislav Lisnić, Catherine I Dumur, Joseph W Landry
Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968536/tumor-vasculature-normalization-by-orally-fed-erlotinib-to-modulate-the-tumor-microenvironment-for-enhanced-cancer-nanomedicine-and-immunotherapy
#7
Qian Chen, Ligeng Xu, Jiawen Chen, Zhijuan Yang, Chao Liang, Yu Yang, Zhuang Liu
The abnormal tumor vasculature is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment (TME). Herein, we uncover that by normalizing the tumor vasculature with erlotinib, a specific inhibitor of epidermal growth factor receptor (EGFR), the tumor perfusion and tumor oxygenation statuses in different types of tumors including murine breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine...
December 2017: Biomaterials
https://www.readbyqxmd.com/read/28955343/inflammasomes-and-cancer-the-dynamic-role-of-the-inflammasome-in-tumor-development
#8
REVIEW
Melvin Kantono, Beichu Guo
Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28953040/novel-therapeutic-agents-in-the-management-of-brain-metastases
#9
Vyshak A Venur, Manmeet S Ahluwalia
PURPOSE OF REVIEW: This review aims to highlight the novel therapeutic agents in the management of brain metastases which are in various stages of clinical development. We review the results from recent clinical trials, publications and presentations at recent national and international conferences. RECENT FINDINGS: Several new systemic treatment options for brain metastases are in early or advanced clinical trials. These drugs have good intracranial and extracranial activities...
August 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28938563/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#10
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew W B Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937963/ki67-and-lymphocytes-in-the-pretherapeutic-core-biopsy-of-primary-invasive-breast-cancer-positive-markers-of-therapy-response-prediction-and-superior-survival
#11
REVIEW
Claus M Schlotter, Lothar Tietze, Ulf Vogt, Carlos Villena Heinsen, Antje Hahn
Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival...
September 22, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28932647/immunotherapy-with-listeria-reduces-metastatic-breast-cancer-in-young-and-old-mice-through-different-mechanisms
#12
Arthee Jahangir, Dinesh Chandra, Wilber Quispe-Tintaya, Manisha Singh, Benson Chellakkan Selvanesan, Claudia Gravekamp
Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#13
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28925066/beyond-the-androgen-receptor-ii-new-approaches-to-understanding-and-treating-metastatic-prostate-cancer-report-from-the-2017-coffey-holden-prostate-cancer-academy-meeting
#14
REVIEW
Andrea K Miyahira, Heather H Cheng, Wassim Abida, Leigh Ellis, Lauren C Harshman, Daniel E Spratt, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. METHODS: The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer...
September 18, 2017: Prostate
https://www.readbyqxmd.com/read/28923310/factors-associated-with-specific-diagnostic-and-statistical-manual-of-mental-disorders-fourth-edition-sexual-dysfunctions-in-breast-cancer-survivors-a-study-of-patients-and-their-partners
#15
Susanna B Hummel, Daniela E E Hahn, Jacques J D M van Lankveld, Hester S A Oldenburg, Eva Broomans, Neil K Aaronson
BACKGROUND: Many women develop sexual problems after breast cancer (BC) treatment. Little is known about BC survivors with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) sexual dysfunction and their partners, and the factors associated with their sexual functioning. AIM: To evaluate (i) patient-related and clinical factors associated with (a) specific DSM-IV sexual dysfunctions and (b) level of sexual functioning and sexual distress as reported by BC survivors and (ii) the association between the sexual functioning of BC survivors and that of their partners...
October 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28919988/identification-of-a-hla-a-0201-restricted-immunogenic-epitope-from-the-universal-tumor-antigen-depdc1
#16
Anna Tosi, Silvia Dalla Santa, Elisa Cappuzzello, Carolina Marotta, Dawid Walerich, Giannino Del Sal, Paola Zanovello, Roberta Sommaggio, Antonio Rosato
The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#17
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916248/breast-cancer-vaccines-delivered-by-dendritic-cell-targeted-lentivectors-induce-potent-antitumor-immune-responses-and-protect-mice-from-mammary-tumor-growth
#18
Paul D Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs...
October 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28915924/pdl1-and-ldha-act-as-cernas-in-triple-negative-breast-cancer-by-regulating-mir-34a
#19
Xiaojia Huang, Xinhua Xie, Hua Wang, Xiangsheng Xiao, Lu Yang, Zhi Tian, Xiaofang Guo, Lijuan Zhang, Hailin Tang, Xiaoming Xie
BACKGROUD: The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. METHODS: Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them...
September 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28914717/the-relationship-between-mismatch-repair-deficiency-and-pd-l1-expression-in-breast-carcinoma
#20
Anne M Mills, Erik A Dill, Christopher A Moskaluk, Jaroslaw Dziegielewski, Tim N Bullock, Patrick M Dillon
Mismatch repair (MMR) deficiency in solid tumors has recently been linked to susceptibility to immunotherapies targeting the programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) axis. Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common. We assessed the relationship between PD-L1 and MMR protein expression by immunohistochemistry in 245 primary and 40 metastatic breast carcinomas...
September 13, 2017: American Journal of Surgical Pathology
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